Variant 17-50707623-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000285243.7(ANKRD40):c.32A>T(p.Gln11Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000609 in 1,598,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

ANKRD40
ENST00000285243.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

Variant links:

Genes affected

ANKRD40 (HGNC:28233): (ankyrin repeat domain 40)

ANKRD40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14060387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD40	NM_052855.4 linkuse as main transcript	c.32A>T	p.Gln11Leu	missense_variant	1/5	ENST00000285243.7	NP_443087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD40	ENST00000285243.7 linkuse as main transcript	c.32A>T	p.Gln11Leu	missense_variant	1/5	1	NM_052855.4	ENSP00000285243	P1
ANKRD40	ENST00000507114.1 linkuse as main transcript	n.33A>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

151764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000426

AC:

AN:

232642

Hom.:

AF XY:

0.000489

AC XY:

AN XY:

126740

show subpopulations

Gnomad AFR exome

AF:

0.0000708

Gnomad AMR exome

AF:

0.000124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000246

Gnomad NFE exome

AF:

0.000830

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000649

AC:

939

AN:

1446760

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

477

AN XY:

719946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000313

Gnomad4 AMR exome

AF:

0.0000918

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000270

Gnomad4 NFE exome

AF:

0.000816

Gnomad4 OTH exome

AF:

0.000301

GnomAD4 genome

AF:

0.000230

AC:

AN:

151882

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000519

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000560

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.32A>T (p.Q11L) alteration is located in exon 1 (coding exon 1) of the ANKRD40 gene. This alteration results from a A to T substitution at nucleotide position 32, causing the glutamine (Q) at amino acid position 11 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

0.021

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.57

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.28

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.28

Vest4

0.52

MVP

0.62

MPC

0.29

ClinPred

0.38

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over